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The Scoop on Poop: Diagnostic and Therapeutic Approach to the Diarrheic Dog and Cat

Stanley L. Marks, BVSc, PhD, Dipl. ACVIM (Internal Medicine, Oncology), Dipl. ACVN
University of California, Davis, School of Veterinary Medicine, Davis, CA, USA

Diarrhea is generally regarded as the most consistent clinical sign of intestinal disease in the dog
and cat. The history and physical examination are paramount for determining whether the
diarrhea is due to primary disease of the gastrointestinal tract or secondary to extraintestinal
diseases such as chronic renal failure or hyperthyroidism.

HISTORY

The history can indicate the location, severity, and probable cause of the disease process. An
important goal of the history is to categorize the diarrhea into small bowel or large bowel in
origin, because this will have a direct impact on the diagnostic and therapeutic approach to the
patient. A careful history should also indicate the presence of extraintestinal disease as the
underlying cause of diarrhea or may identify important predisposing factors, such as diet,
environmental factors, exposure to parasites, infectious agents, drugs or toxins. The history
should focus on the duration of the diarrhea, the patients diet (and diet changes), the
appearance of the faeces (color, volume, mucus, presence of fresh blood), worming and
vaccination history, defecation frequency, aggravating or alleviating factors, and defecation
urgency. Adverse reactions to food are a relatively common cause of chronic diarrhea in dogs
and cats, and the history is a simple way to determine incriminating diets or protein sources.

PHYSICAL EXAMINATION

Physical examination should emphasize the detection of fever, cachexia, dehydration, weakness
or depression, pallor (blood loss anemia) and effusions or edema (hypoalbuminemia). Intestinal
loops should be carefully palpated for masses, thickening (inflammatory or neoplastic
infiltration), distension, pain, or associated lymphadenopathy. Palpation of the rectum may
reveal rectal masses or thickening of the rectal wall.

DIAGNOSTIC APPROACH

For undiagnosed chronic diarrhea, the minimum database should include a complete blood count
(CBC), a serum biochemistry profile, a urinalysis, a fecal floatation for parasitic ova, and a direct
smear of saline admixed fresh feces for protozoa. Fecal flotations should always be done on
fresh fecal specimens (< 1 hour ideally), or on fresh fecal specimens that have been refrigerated
for < 48 hrs. Flotations are excellent for recovering common nematode ova, oocysts of coccidia,
and Giardia cysts. The main limitation of flotations is their inability to float organisms whose
diagnostic stage has a specific gravity higher than that of the flotation medium. Most commonly
these are the heavy ova of trematodes and acanthocephalans (thorny-headed worms). Fragile
cysts and larvae, though recovered, may be too distorted to identify. It is always preferable to
use a centrifugation flotation technique. This is probably the single most important change one
can institute to improve routine recovery of parasite stages by flotation. Flotation methods that
do not utilize a centrifugation technique are often not sensitive enough to recover small numbers
of organisms in the feces. Always use a coverslip rather than a loop or glass rod to transfer the
meniscus to a slide. If your centrifuge has free-swinging buckets, use a coverslip on the final
centrifugation to recover parasites. If your centrifuge has a fixed-angle, carefully add more
flotation medium after the final spin to create a meniscus and set the coverslip on top for several
minutes before lifting it off for examination. If at this point you are still determined to do
standing flotations, use a coverslip to transfer the meniscus. Coverglass improves the optics of
any microscope. Check the specific gravity of flotation medium. If possible, switch to zinc
sulphate (sg 1.18 or 1.2) in order to improve detection and morphology of Giardia spp.
Remember that regardless of the flotation solution all eggs do not float. Choice of flotation
solution is less important than the actual method of flotation. Examine preparations as soon as
possible after preparing them. Delay will result in distortion of some parasite stages and
incorrect or missed diagnoses, especially with delicate cysts and oocysts.

Encysted forms of Giardia organisms in a fecal specimen may be detected most reliably with
zinc sulfate floatation, as opposed to examination of fresh saline smears.1 Preliminary studies in
Giardia-infected cats at the University of California, Davis, have revealed that the ProSpecT
Microplate ELISA Assay compares favorably in sensitivity and specificity to the zinc sulfate
floatation technique; however, the sensitivity of the ProSpecT Giardia Rapid ELISA Assay is
significantly less than that of the Microplate Assay and zinc sulfate floatation methods. The
importance of evaluating 2 to 3 consecutively obtained fecal specimens cannot be
overemphasized as our studies in dogs and cats have confirmed intermittent shedding of oocysts,
and significant increases in sensitivity in all diagnostic tests when more than one stool specimen
is examined.

Direct wet mounts (direct smears) should be performed on all diarrheic specimens. The study
must be done on fresh feces (< 1 hour) to prevent desiccation of motile trophozoites, and to
preserve motility of the organism for detection. Morphological differentiation of Giardia
trophozoites from Tritrichomonas foetus trophozoites can be difficult in unstained smears.
Giardia trophozoites typically have a falling leaf motion, whereas T. foetus trophozoites have
an irregular hap-hazard motion. Diagnosis of T. foetus can also be facilitated by implementation
of a commercially available culture system, which is specific for growth of T. foetus.
Tritrichomonas foetus has been associated with a large-bowel type diarrhea in dogs and cats,
which has been shown to be refractory to antibiotic therapy.

Macroscopic examination of a fresh fecal specimen is essential for assessment of bulk, color,
consistency, and detection of blood and mucus. Small bowel diarrhea is generally free of grossly
visible mucus or red blood, but prominent steatorrhoea may cause the faeces to appear lighter in
color. Rapid intestinal transit time can be associated with yellow or green stools due to
incomplete metabolization of bilirubin.2

The complete blood count may reveal an eosinophilia secondary to endoparasitism, eosinophilic
enteritis, or abdominal mast cell neoplasia. Anemia may result from enteric blood loss or from
depressed erythropoiesis caused by systemic disease or chronic inflammation. Underlying
systemic diseases such as chronic renal failure or liver disease may be detected on the serum
biochemical profile. In addition, panhypoproteinemia (low serum albumin and globulin) may be
seen with severe infiltrative bowel diseases such as inflammatory bowel disease, intestinal
lymphoma, and Histoplasmosis. The finding of steatorrhoea and weight loss in the face of a
normal to increased appetite is consistent with a malassimilation disorder such as exocrine
pancreatic insufficiency. This disorder is best confirmed by performing a serum trypsin-like
immunoreactivity assay.3 Animals exhibiting signs of large bowel diarrhea should have a rectal
scraping and stained fecal smear performed to evaluate for inflammatory cells or fungal hyphae.4

Survey abdominal radiographs are a relatively low yield procedure in most patients with chronic
diarrhea, but are indicated in dogs suspected of having partial obstructions due to foreign bodies,
intussusceptions, or masses. Abdominal ultrasound is complimentary to survey abdominal
radiographs and is more sensitive for the detection of abdominal masses, intestinal mural
thickening, intussusceptions, and mesenteric lymphadenopathy.5 In addition, ultrasound-guided
percutaneous biopsy or aspiration of masses is an effective diagnostic procedure. Contrast
radiography and fluoroscopy are occasionally indicated for identification of partial obstructions
and intestinal motility disorders, respectively.

The clinical documentation of intestinal bacteria causing diarrhea in dogs is clouded by the
occasional presence of these organisms existing as normal constituents of the indigenous
intestinal flora. Fecal isolation of Clostridium perfringens and C. difficile is therefore a low-
yield procedure in animals with diarrhea, and commercially available toxin assays are
recommended. Fecal cultures are best performed to isolate Campylobacter spp. and Salmonella
spp.6-9 Fecal enteric panels should be reserved for dogs and cats developing diarrhea after
kenneling or show attendance, in animals with an acute onset of bloody diarrhea in association
with evidence of sepsis, or in diarrhea outbreaks occurring in more than one pet in a household.
Caution should be exercised when interpreting the presence of C. perfringens endospores in fecal
smears obtained from animals with diarrhea, because healthy dogs can harbor large numbers of
C. perfringens endospores in their stools. In addition, the currently accepted opinion that 2 to
3 endospores/oil immersion field is associated with enterotoxin appears unsubstantiated in light
of recent studies documenting a poor correlation between fecal endospore numbers and the
presence of enterotoxin.10

Dogs and cats with no evidence of life-threatening disease, whose diarrhea remains undiagnosed
after initial laboratory and imaging procedures, are further evaluated with elimination diets for 2
to 3 weeks. The diet selected should be free of additives and preservatives, and contains a novel
protein source that is highly digestible. The protein should be highly digestible because intact
proteins are far more antigenic than polypeptides and amino acids. If signs resolve following
several weeks of dietary therapy, the diet should be balanced or alternatively a complete and
balanced commercial diet with the same novel protein source as the home-made diet should be
selected. Hydrolyzed protein diets are commercially available and appear beneficial for some
patients refractory to controlled diets containing intact protein sources. If signs do not resolve, a
more extensive diagnostic approach is warranted.

Endoscopy is a valuable procedure for the diagnosis of intestinal mucosal diseases that are
associated with morphologic changes. Endoscopy, however, does not differentiate intestinal
motility disorders, secretory diarrheas, or brush border enzyme defects, and is likely to miss
lesions in the intestinal submucosa and muscularis. In addition, endoscopy is limited by the
working length of the scope, limiting endoscopic examination of the jejunum. Rigid proctoscopy
is preferred over flexible colonoscopy for the initial evaluation of large bowel disease. Rigid
proctoscopy entails less risks, time, and cost than colonoscopy, and is able to diagnose the
majority of large bowel disorders because of the diffuse nature of the disease. Flexible
colonoscopy is indicated for evaluation of upper colonic disease, including cecal inversion,
ileocolic neoplasia, and occult Trichuris infection.

Tests for malabsorption do not give a specific causal diagnosis for the diarrhea, and many of
these tests are limited by relatively poor sensitivity and specificity. In contrast to the endoscopic
procedure that typically diagnoses abnormal mucosal morphology, malabsorption tests evaluate
intestinal function. They identify abnormal carbohydrate or fat assimilation secondary to
motility disorders, bacterial overgrowth, or brush border enzyme deficiencies. Screening tests of
malassimilation include the indirect quantitative analysis of fecal fat; the breath hydrogen
analysis, and the direct/indirect Sudan stain for fecal fat. The use of the fat absorption test and
Sudan stain for fecal fat are not recommended due to the insensitivity of the tests and frequency
of misleading results.

PRINCIPLES OF DIARRHEA THERAPY

Symptomatic therapy includes restoration and maintenance of fluid and electrolyte balance,
dietary modification, and empiric deworming. Antibiotics and immunosuppressive drugs are
introduced based on evidence of inflammatory bowel disease or bacterial enteritis. Motility
modifiers are only indicated if the diarrhea is intractable and should not be used if the diarrhea is
due to invasive microorganisms. The opiate and opioid narcotic analgesics such as loperamide
(Imodium; 0.1-0.2 mg/kg TID, PO) are the most effective motility modifiers for managing
diarrhea. Anticholinergic agents are contraindicated because they may cause generalized
suppression of all motility and may potentiate ileus. Most dogs with moderate to severe
inflammatory bowel disease (IBD) will require adjuvant pharmacologic therapy in combination
with dietary management. It is important to understand that the therapy of IBD must be tailored
according to each patients response.

Antibiotics

Use of antibiotics as empirical therapy in the management of uncomplicated or noninfectious


diarrhea is not recommended because of the adverse effects of the antibiotics on the normal
intestinal microflora and their tendency to promote resistant strains of bacteria. Antibiotics are
indicated when specific bacterial or protozoan enteropathogens, such as Campylobacter,
Clostridium, or Giardia are isolated from the feces (Table 1). In addition, antibiotics should be
considered in conditions associated with severe mucosal damage and a high risk of secondary
sepsis or endotoxemia.2 Metronidazole (Flagyl) has several beneficial properties, including
broad spectrum activity against anaerobic bacteria, antiprotozoal activity, and potent inhibition
of cell-mediated immunity. Metronidazole may be used as a single agent in mild cases of IBD;
however, it should be combined with prednisone to manage moderate to severe cases or to allow
a reduction in prednisone dosage. The dose of metronidazole is 10 to 15 mg/kg q 8 to 12 hours.
Metronidazole is supplied as 250 and 500 mg tablets or as a 5 mg/ml oral suspension.
Metronidazole tablets have a sharp, unpleasant, metallic taste when scored that can cause severe
salivation. Scored tablets can be placed in empty gelatin capsules or compounded into a
palatable suspension to minimize this problem from occurring. Side- effects are rare, although
metronidazole has been associated with a peripheral neuropathy in both humans and dogs, and
less commonly in cats. Less common side effects include inappetence, nausea, vomiting, ataxia,
seizures, and reversible neutropenia. Tylosin (Tylan) is a macrolide antibiotic that has been
reported to be effective in managing canine IBD. Although the drugs mechanism of action is
unknown, it appears to be effective in some dogs refractory to other forms of therapy. Tylosin is
supplied in a highly concentrated powdered form (approx. 3.5 g per teaspoon) marketed for
poultry. The dose range is 15 to 20 mg/kg q 12 hours. Tylosin appears safe and no side effects
have been reported.

Immunosuppressive Drugs

Corticosteroids
The main indication for corticosteroid administration appears to be in dogs and cats with
lymphoplasmacytic or eosinophilic gastroenteritis, and in dogs with colitis that is only partially
responsive to sulfasalazine or metronidazole.12,13 Prednisone is the corticosteroid most
frequently used for the therapy of canine and feline IBD. The dosage and duration of therapy is
based on the severity and duration of clinical signs, the severity and type of inflammation, the
clinical response, and tolerance to the drug. The initial dosage of prednisone for therapy of IBD
in dogs is 1 to 2 mg/kg q 12 hours. The drug is gradually tapered over a 4- to 10-week period
once clinical remission is attained. Some dogs will require higher dosages to maintain clinical
remission; however, the deleterious side effects of prednisone in dogs (polyuria, polydipsia,
polyphagia, weakness, and other clinical signs of iatrogenic hyperadrenocorticism) often
preclude its prolonged administration. Combination therapy with a controlled diet, azathioprine,
or metronidazole is undertaken with the goal of reducing the dose of prednisone.

Poorly absorbed oral steroids have been developed for human patients to reduce the systemic
side effects of oral glucocorticoids. Budesonide, an orally administered corticosteroid
-hydroxyprednisolone, has high topical anti-inflammatory activity and
low systemic activity because of its high affinity to the steroid receptor and rapid hepatic
conversion to metabolites with minimal or no steroid activity. Controlled prospective clinical
trials comparing the efficacy of prednisone versus budesonide in dogs with IBD are warranted
before the routine use of this drug can be recommended. Parenteral corticosteroid therapy is
reserved for vomiting patients, or animals with severe nonresponsive disease. Depot
preparations of glucocorticoid should be avoided because of their rapid and severe depression of
the hypothalamo-pituitary axis and their inconsistent control of clinical signs in animals with
moderate to severe IBD. In glucocorticoid resistant cases, the addition of metronidazole14 or
chlorambucil (Leukeran) may result in remission of disease.

Azathioprine
Azathioprine is an antimetabolite that is converted to 6-mercaptopurine in the liver and then to
thioinosinic acid. The latter compound impairs purine biosynthesis and this biochemical reaction
inhibits cellular proliferation and reduces natural killer cell cytotoxicity. The onset of these
immunological effects is slow, paralleling the human clinical data which shows benefits for these
drugs when given for 3 to 6 months or longer. Despite the lack of clinical trials showing efficacy
of azathioprine in the treatment of canine and feline IBD, clinical and anecdotal experience
suggests that the drug is most useful in dogs as adjunctive therapy in severe or refractory IBD.
Azathioprine can also be used for its steroid-sparing effects when the adverse effects of
prednisone are unacceptably high. The dose for dogs is 50 mg/m2 or 1-2 mg/kg once daily for 2
weeks, followed by alternate-day administration. The most significant side effect of azathioprine
is bone marrow suppression, particularly in cats. Frequent haematologic monitoring is warranted
with temporary discontinuation of the drug if thrombocytopenia or neutropenia develop. Other
side effects include anorexia, pancreatitis, and hepatic dysfunction.

Sulfasalazine
The drug consists of sulfapyridine linked to mesalamine (previously called 5-aminosalicylic
acid) by an azo bond and is poorly absorbed in the upper gastrointestinal tract. In humans,
approximately 75% of sulfasalazine passes unabsorbed to the colon, where bacterial
azoreductases cleave the azo bond and release the active moiety of the drug, mesalamine.
Sulfapyridine is almost completely absorbed in the colon, metabolized in the liver, and excreted
in the urine. The mesalamine moiety is locally absorbed and acetylated in the cytosol of the
colonic epithelial cell and inhibits the formation and degradation of inflammatory mediators,
including leukotrienes, prostaglandins, thromboxane, platelet activating factor, histamine, and a
number of cytokines, including interleukin 1-alpha and interferon-gamma. Sulfasalazine is of no
value in managing small bowel inflammation because colonic bacterial metabolism is needed to
release the active moiety. Sulfasalazine is supplied as 500-mg tablets or as a 50-mg/ml liquid
formulation. The usual initial dose in dogs is 20 to 40 mg/kg q 8 hours for 3 weeks, followed by
20 to 40 mg/kg q 12 hours for 3 weeks, and 10 to 20 mg/kg q 12 hours for 3 weeks. The most
common side-effects of sulfasalazine include anorexia, vomiting, cholestatic jaundice, allergic
dermatitis, and keratoconjunctivitis sicca (KCS). These side effects have been attributed to the
sulfapyridine moiety; however, studies in beagles have documented the association of KCS with
mesalamine administration.

Dietary therapy

Elimination Diets
Several studies in the veterinary literature suggest that some patients may benefit from diets
providing novel, highly digestible protein sources. Selecting a protein source not commonly
found in the animals diet is recommended because it reduces the likelihood of feeding a protein
to which the animal is allergic. The ideal elimination diet for dogs with chronic small bowel
diarrhea is based on a highly digestible single protein and carbohydrate source that is gluten and
lactose free. There are a number of commercially available elimination diets that can be utilized.
The use of computer-generated home-made diets formulated by a qualified veterinary nutritionist
is typically reserved for cats failing to respond to the commercial diets. It is important that the
ingredients list of a potentially hypoallergenic diet be thoroughly evaluated, because diets with
several protein sources (lamb, beef, rice, and wheat) are commonly marketed with a claim to
hypoallergenicity.

Dietary recommendations for the management of large bowel diarrhea are controversial. The
response to dietary therapy can vary dramatically from one patient to another, with some animals
showing improvement on low residue, hypoallergenic diets, and others improving on less
digestible diets containing soluble or insoluble fiber sources.15,16 There is evidence to suggest
that some forms of colitis may be associated with a dietary sensitivity similar to that observed
with small bowel disease. The theoretical benefit for utilizing highly digestible hypoallergenic
diets for patients with colitis includes reducing the digestive challenge to the large intestine and
minimizing the likelihood of dietary antigens actually reaching the colon, thus lessening the
likelihood of an immunological reaction.17 The author utilizes the same elimination diets for
large intestinal disease as those recommended for management of small-bowel type disease. The
supplementation of fermentable fiber sources such as psyllium or oat bran may be necessary in
cats with large-bowel type disease showing partial resolution of their clinical signs. Failure to
respond to these recommendations may necessitate selecting a hypoallergenic diet with a
different novel protein source or adding insoluble fiber to the diet.

Dietary Fiber
There is increasing evidence that fermentable fiber sources can also be beneficial because of
their pre-biotic effect in reducing or preventing inflammation in experimental models of IBD.
Therefore, a fermentable fiber source should probably be included as part of dietary therapy,
although information regarding which (e.g. resistant starch, fructosoligosaccharides, inulin) and
how much is lacking. Fructooligosaccharides (FOS) are carbohydrates that resist digestion by
the enzymes in the gastrointestinal tract and can be metabolized by the microbial species that
colonize the distal small intestine and colon. The addition of FOS to feline diets at 0.75% (DM)
did not affect duodenal flora, but it did increase the numbers of lactobacilli and reduce the
numbers of E. coli in the fecal flora of healthy cats.18,19

Recently, treatment of chronic idiopathic large bowel diarrhea with a highly digestible diet and
soluble fiber was reviewed in a retrospective study of 37 dogs. Treatment with a soluble fiber
source (Metamucil), added to a highly digestible diet, resulted in a very good to excellent
response in 23 of the 27 dogs that received supplementation. Dogs classified as having a very
good or excellent response to soluble fiber supplementation received no other additional therapy
except for occasional loperamide or diphenoxylate. Fiber supplementation was later reduced or
eliminated in 11 dogs; diarrhea returned in 6 of them.
Polyunsaturated fatty acids
Fish oil has been reported to be beneficial in ulcerative colitis and Crohns disease patients, but
the results are controversial. Only two of these studies found significant decreases in rectal
leukotriene B4 (LTB4) concentrations, the others simply reported clinical improvement. The
differences between the reports regarding study design, supplement composition, dose and
assessment of clinical improvement may in part explain the conflicting results. A recent study
compared the efficacy of n-3 fatty acids in fish oil to sulfasalazine in the treatment of mild to
moderate active ulcerative colitis in humans. Treatment with n-3 fatty acids resulted in greater
disease activity as detected by a significant increase in platelet count, erythrocyte sedimentation
rate, C-reactive protein, and total fecal nitrogen excretion. An often overlooked concern is the
increase in lipid peroxidation after fish oil supplementation is instituted. Antioxidant
supplementation may be able to counteract the potentially adverse effects of n-3 fatty acids.
Most of the literature regarding n-3 fatty acid administration fails to address the amount of
attendant antioxidant supplementation. There are no reports in the veterinary literature to date
demonstrating the efficacy of n-3 fatty acid supplementation in managing canine or feline
patients with IBD. Studies in healthy dogs fed diets with n-6 to n-3 ratios of 5:1 and 10:1
demonstrated a decreased production of LTB4 in plasma, neutrophils and skin. Increases in
certain long chain n-3 fatty acids and decreases in arachidonic acid were identified in the small
intestine and colonic mucosa of healthy Beagles fed the same ratios. Further research is
necessary to determine the clinical benefits in dogs and cats with large bowel diseases.

Vitamin B12
Low serum B12 or cobalamin has often been regarded solely in the context of its diagnostic
utility in identifying dogs with small intestinal bacterial overgrowth. However, low serum B12
has been described in dogs and cats in association with a wide variety of gastrointestinal diseases
including IBD and intestinal lymphoma.20 It is likely that mucosal repair is impeded in the initial
management of IBD when B12 is deficient and its absorption impaired, however this has not
been investigated. Consideration should be given to B12 assays in the initial evaluation of cats
with chronic intestinal disease, and parenteral administration during the initial management of
IBD if low serum cobalamin is identified. Dogs are typically supplemented with B12 at a dose
of 5001000g per dose, subcutaneously, for 4 to 5 weeks on a weekly basis. Serum
concentrations of B12 should be rechecked q 3-4 months if clinical signs of diarrhea are still
persistent, or alternatively, B12 can be empirically administered at the same dose.

Water-soluble vitamins are often depleted by the fluid losses associated with diarrhea and fat-
soluble vitamin loss can be significant in animals with steatorrhoea. Deficiencies of vitamins A,
C, D, E and have been reported in the human literature. Common mineral deficiencies in
patients with ulcerative colitis and Crohns disease include selenium, zinc and magnesium.
Published recommendations for vitamin B12, K and E supplementation in gastrointestinal disease
are available, but further investigation into vitamin and mineral status and requirements for dogs
with IBD is warranted.

TABLE 1

ANTIBIOTICS FOR TREATMENT OF BACTERIAL-ASSOCIATED DIARRHEAS


Drug Dose Indications
Enrofloxacin 5 mg/kg BID, PO Sepsis (Gram negative bacteria)
Enrofloxacin 5 mg/kg BID, PO Campylobacter spp.
Erythromycin 10-15 mg/kg TID, PO Campylobacter spp.
Ampicillin 10-20 mg/kg TID, PO Clostridium perfringens
Ampicillin 10-20 mg/kg TID, IV, SC Sepsis (use with aminoglycosides)
Gentamicin 2.2 mg/kg TID, IV, SC Sepsis
Cephalothin 22-44 mg/kg TID, IV, IM Sepsis
Metronidazole 10-15 mg/kg BID, PO C. perfringens, C. difficile, IBD
Tylosin 15 mg/kg SID-BID, PO C. perfringens, IBD
Trimethoprin-sulfa 15 mg/kg BID, PO, IV, SC Salmonella spp.
Enrofloxacin 5 mg/kg BID, PO Salmonella spp.
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